The polymorphic inversion on 17q21, that includes the MAPT gene, represents a unique locus in the human genome characterized by a large region with strong linkage disequilibrium. Two distinct haplotypes, Hl and H2, exist in modern humans, and Hl has been unequivocally related to several neurodegenerative disorders. Recent data indicate that recurrent inversions of this genomic region have occurred through primate evolution, with the H2 haplotype being the ancestral state. Neandertals harbored the H1 haplotype; however, until now, no data were available for the Denisova hominin. Neandertals and Denisovans are sister groups that share a common ancestor with modern humans. We analyzed the MAPT sequence and assessed the differences between modern humans, Neandertals, Denisovans, and great apes. Our analysis indicated that the Denisova hominin carried the H1 haplotype, and the Neandertal and Denisova common ancestor probably shared the same subhaplotype (H1j). We also found 68 intronic variants within the MAPT gene, 23 exclusive to Denisova hominin, 6 limited to Neandertals, and 24 exclusive to present-day humans. Our results reinforce previous data; this suggests that the 17q21 inversion arose within the modern human lineage. The data also indicate that archaic hominins that coexisted in Eurasia probably shared the same MAPT subhaplotype, and this can be found in almost 2% of chromosomes from European ancestry.

¹Single nucleotide polymorphisms (SNPs) with large allele frequency differences between human populations are relatively rare. The longest run of SNPs with an allele frequency difference of one between the Yoruba of Nigeria and the Han Chinese is found on the long arm of the X chromosome in the intergenic region separating the EDA2R and AR genes. It has been proposed that the unusual allele frequency distributions of these SNPs are the result of a selective sweep affecting African populations that occurred after the out-of-Africa migration. To investigate the evolutionary history of the EDA2R/AR intergenic region, we characterized the haplotype structure of 52 of its highly differentiated SNPs. Using a publicly available data set of 3,000 X chromosomes from 65 human populations, we found that nearly all human X chromosomes carry one of two modal haplotypes for these 52 SNPs. The predominance of two highly divergent haplotypes at this locus was confirmed by use of a subset of individuals sequenced to high coverage. The first of these haplotypes, the α-haplotype, is at high frequencies in most of the African populations surveyed and likely arose before the separation of African populations into distinct genetic entities. The second, the β-haplotype, is frequent or fixed in all non-African populations and likely arose in East Africa before the out-of- Africa migration. We also observed a small group of rare haplotypes with no clear relationship to the α- and β-haplotypes. These haplotypes occur at relatively high frequencies in African hunter-gatherer populations, such as the San and Mbuti Pygmies. Our analysis indicates that these haplotypes are part of a pool of diverse, ancestral haplotypes that have now been almost entirely replaced by the α- and β-haplotypes. We suggest that the rise of the α- and β-haplotypes was the result of the demographic forces that human populations experienced during the formation of modern African populations and the out-of-Africa migration. However, we also present evidence that this region is the target of selection in the form of positive selection on the α- and β-haplotypes and of purifying selection against α/β recombinants.

The San and Khoe people currently represent remnant groups of a much larger and widely distributed population of hunter-gatherers and pastoralists who had exclusive occupation of southern Africa before the arrival of Bantu-speaking groups in the past 1,200 years and sea-borne immigrants within the last 350 years. Genetic studies [mitochondrial deoxyribonucleic acid (DNA) and Y-chromosome] conducted on San and Khoe groups revealed that they harbor some of the most divergent lineages found in living peoples throughout the world. Recently, high-density, autosomal, single-nucleotide polymorphism (SNP)-array studies confirmed the early divergence of Khoe-San population groups from all other human populations. The present study made use of 220 autosomal SNP markers (in the format of both haplotypes and genotypes) to examine the population structure of various San and Khoe groups and their relationship to other neighboring groups.

Acid phosphatase (ACP₁) is a polymorphic enzyme that catalyzes the conversion of flavin-mononucleotide (FMN) to riboflavin and regulates the cellular concentration of flavin-adenine-dinucleotide (FAD) and, consequently, energy metabolism. Its activity is modulated by adenosine deaminase locus 1 (ADA₁) genotype. The aim of our work is to verify whether individuals with a high proportion of ACP₁ f-isozyme and carrying the ADA₁ *2 allele, displaying the highest phosphatase activity, may have a higher life expectancy.

Genomic DNA was extracted from the peripheral blood of 569 females and 509 males (18 to 106 years of age) randomly recruited from Central Italy. These samples were subdivided into three sex-specific age groups (the ages of women are in square bracket): Class 1: age <66 [<73]; Class 2: ages 66 to 88 [73 to 91]; Class 3: age >88 [>91]. ACP₁ and ADA₁ singlenucleotide polymorphisms (SNPs) were genotyped by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) methods and statistical analyses were performed with SPSS 14.0. The results showed a larger proportion of Class 3 individuals displaying high ACP₁ f-isozyme concentration and carrying the ADA₁ *2 allele than those individuals of Class 2 and Class 2 plus Class 1. Thus, we postulate that in Class 3 individuals the high phosphatase activity, resulting from the combined presence of high ACP₁ f-isozyme concentration and the ADA₁ *2 allele, lowers the rate of glycolysis that may reduce the amount of metabolic calories and, in turn, activate Sirtuin genes that protect cells against age-related diseases.

We reviewed data collected during several studies concerning the genetic isolate of Carloforte (Sardinia, Italy) and analyzed new data on Y-chromosome markers. Carloforte is also a language island, where people still speak Tabarchino, an archaic form of Ligurian dialect. Demographic data indicate that, in the early years of its history, the Carloforte population was characterized by a high degree of endogamy and consanguinity rates that started to decrease around 1850, when marriages with Sardinian people began to occur more frequently. Cultural factors, mainly language, account for the high endogamy. Genetic data from classical markers, mtDNA, and Y-chromosome markers confirmed the strong isolation of the Carloforte population, which appears significantly different from the neighboring population of Sardinia. Analysis of mtDNA emphasizes the crucial aspect of sampling strategy—two different samplings of the same population (one based on founder surnames; the other one based on grandparents' criterion) gave different results. Founder surnames sampling is not affected by recent events, and therefore it better describes the ancestral population, whereas, grandparents' criterion sampling gives a picture of the present population, shaped by more recent events, such as migration and gene flow. This review further supports the notion that a comprehensive approach, including a detailed knowledge of the history of the population and the collection of different samplings, is essential in anthropology for reconstructing past and recent events that contributed to establishing the present genetic structure of the population. Likewise, it is essential in medical genetics to identify genes involved in complex diseases. An ideal scenario is offered by a genetic isolate with a recent, and well-documented, history, such as Carloforte, that can be a paradigm for this type of investigation.

We use two coupled equations to analyze the space/time dynamics of two interacting languages. First, we introduce a cohabitation model, which is more appropriate for human populations than classical (noncohabitation) models. Second, using numerical simulations, we find the front speed of a new language spreading into a region in which another language was previously used. Third, for a special case, we derive an analytical formula that makes it possible to check the validity of our numerical simulations. Finally, as an example, we find that the observed front speed for the spread of the English language into Wales in the period 1961 through 1981 is consistent with the model predictions. We also find that the effects of linguistic parameters are much more important than the effects of parameters related to population dispersal and reproduction. If the initial population densities of both languages are similar, they have no effect on the front speed. We outline the potential of the new model to analyze relationships between language replacement and genetic replacement.